In recent years, research related to surface plasmon resonance sensor using resonance excitation of a surface plasmon wave, which exists on a surface of a metal, by light has been advanced as one of the high sensitivity sensing systems. The wave number of the surface plasmon wave on a surface of the metal is determined by a dielectric constant of a medium that contacts the surface of the metal.
In a surface plasmon resonance sensor using surface plasmon resonance (SPR) in a metal thin film covering one aspect of a prism, since a surface plasmon wave cannot be excited by light that propagates through the air, evanescent light, which is generated at the time of total reflection and which is non-propagating light, is used. Therefore, such a sensor needs a total reflection optical system for generating the evanescent light. A surface plasmon resonance sensor, which excites a surface plasmon wave by stacking a metal thin film, a dielectric thin film, and a metal thin film in this order on a prism, and making light from a light source totally reflect on the metal thin film, is disclosed in Japanese Patent Application Laid-Open No. H10-267841.
A localized plasmon is excited by making light, spreading the air, enter nanometer size of metal structure. Hence, a sensor using the localized plasmon does not need a total reflection optical system, but is applicable to various forms of sensors. There is a known measuring method in which metal fine particles are fixed on a substrate surface and a substance near the metal fine particles is detected using the induced localized plasmon resonance. When light is incident onto metal fine particles, such as gold or silver, a characteristic resonance spectrum is produced by the localized plasmon resonance. The absorbance at a resonance peak becomes larger as a dielectric constant of a medium near the metal fine particles becomes larger and shifts toward a long wavelength.
The specification of Japanese Patent No. 3452837 discloses a sensor constructed using a plurality of metal fine particles arranged on a substrate in isolation from each other. Here, the localized plasmon resonance sensor, which detects a refractive index of a medium near the fine particles by radiating light on a sensor unit and measuring an absorbance of light that permeates the sensor unit, is disclosed. Specifically, a system using a gold colloid about 20 nm in diameter is proposed. In addition, European Patent Application Publication No. 1445601A2 discloses a localized plasmon sensor, which has a layer-like substrate in which a plurality of micropores are formed, metal fine particles are filled in the micropores, and a metal thin film is arranged around the micropores on a surface of the substrate. It is described that this sensor can detect a minute refractive index change and binding with specified substances by using an interaction between localized plasmon resonance of fine particles and surface plasmon resonance of the nearby metal thin film.
On the other hand, as proposed by Felicia Tam et al. (J. Phys. Chem. B., 2004, Vol. 108, No. 45, p. 17290-17294), there is an example of a device structure that aims to enhance the detection capability by producing core shell type fine particles that are made by coating gold thin films on dielectric cores.
There is disclosed, in European Patent Application Publication No. 0965835A2, a system in which an interaction between a metal thin film and metal fine particles is used. Here, a sensor system combining a gold thin film formed on a substrate and gold-coated fine particles of a polymer formed on the gold thin film is proposed. This system is aimed at enhancing sensor characteristics by the interaction between surface plasmon resulting from the gold thin film of a foundation and localized plasmon resulting from the gold coating on surfaces of the fine particles of the polymer.
Since a measuring method using localized plasmon resonance does not need tagged molecules, such as fluorophores, the assay procedure is simple in comparison with a fluorescent immunoassay or a chemiluminescence immunoassay. In addition, since direct real-time monitoring of a process of an adsorption reaction on surfaces of metal fine particles is possible, applications in various kinds of assays are expected. Nevertheless, sufficient detection sensitivity was not obtained in affinity assays, such as an immunoassay, using those conventional target substance detecting devices that employ plasmon resonance.